PMID- 30952530
OWN - NLM
STAT- MEDLINE
DCOM- 20200212
LR  - 20200212
IS  - 1874-1754 (Electronic)
IS  - 0167-5273 (Linking)
VI  - 286
DP  - 2019 Jul 1
TI  - NETosis is associated with the severity of aortic stenosis: Links with 
      inflammation.
PG  - 121-126
LID - S0167-5273(18)36512-4 [pii]
LID - 10.1016/j.ijcard.2019.03.047 [doi]
AB  - BACKGROUND: An involvement of neutrophil extracellular traps (NETs) in the aortic 
      stenosis (AS) pathogenesis is unknown. METHODS: We enrolled 50 patients, median 
      age 66.5 years with isolated severe AS, after aortic valve replacement and 20 
      healthy sex/age-matched controls. Autopsy-derived aortic valves from 5 healthy 
      donors served as controls. Valvular expression of citrullinated histone H3 
      (citH3), myeloperoxidase (MPO), and neutrophil elastase (NE) and macrophages 
      (CD68) were evaluated by immunostaining. Plasma citH3 and interleukin 6 (IL-6) 
      were also determined. RESULTS: All stenotic and healthy valves expressed citH3 in 
      the leaflets' endothelial and sub-endothelial layers at the aortic side. Amount 
      of valvular citH3-positive cells was higher in AS patients compared with controls 
      (53.5 [33-62]% vs. 5.7 [4.1-9.0]%, p < 0.0001) and correlated with aortic valve 
      area (AVA; r = -0.69, p < 0.0001) and mean transvalvular gradient (r = 0.6, 
      p < 0.0001). Double-staining revealed that in AS valves 27.2 +/- 9.8% of cells were 
      citH3/MPO- and 25.3 +/- 8.9% citH3/NE-positive. Within stenotic valves, 6.4 +/- 2.5% 
      of cells showed citH3/CD68 double-positivity and were identified as macrophages. 
      AS patients compared to controls had 83% higher plasma citH3 (p < 0.0001). In AS, 
      plasma citH3 correlated with IL-6 (r = 0.39, p = 0.0054) levels and AVA 
      (r = -0.45, p = 0.0009). CONCLUSIONS: The presence of NETs in stenotic valves and 
      association with AS severity suggest novel mechanisms involved in the disease 
      progression.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Kopytek, Magdalena
AU  - Kopytek M
AD  - John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian 
      University Medical College, Krakow, Poland.
FAU - Kolasa-Trela, Renata
AU  - Kolasa-Trela R
AD  - John Paul II Hospital, Krakow, Poland.
FAU - Zabczyk, Michal
AU  - Zabczyk M
AD  - Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
FAU - Undas, Anetta
AU  - Undas A
AD  - John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian 
      University Medical College, Krakow, Poland; Faculty of Medicine and Health 
      Sciences, Jan Kochanowski University, Kielce, Poland.
FAU - Natorska, Joanna
AU  - Natorska J
AD  - John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian 
      University Medical College, Krakow, Poland. Electronic address: 
      j.natorska@szpitaljp2.krakow.pl.
LA  - eng
PT  - Journal Article
DEP - 20190326
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
RN  - 0 (Biomarkers)
RN  - 0 (Histones)
RN  - 0 (Interleukin-6)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
SB  - IM
CIN - J Cardiovasc Pharmacol. 2019 Nov;74(5):367-368. PMID: 31517777
MH  - Aged
MH  - Aortic Valve/*diagnostic imaging
MH  - Aortic Valve Stenosis/*diagnosis/metabolism
MH  - Biomarkers/metabolism
MH  - Disease Progression
MH  - Echocardiography
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Traps/*metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Histones/blood
MH  - Humans
MH  - Immunoturbidimetry
MH  - Inflammation/*metabolism
MH  - Interleukin-6/blood
MH  - Leukocyte Elastase/blood
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/*metabolism
MH  - Peroxidase/blood
MH  - Prognosis
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Aortic stenosis
OT  - Citrullinated histones
OT  - Myeloperoxidase
OT  - Neutrophil elastase
OT  - Neutrophil extracellular traps
EDAT- 2019/04/07 06:00
MHDA- 2020/02/13 06:00
CRDT- 2019/04/07 06:00
PHST- 2018/11/08 00:00 [received]
PHST- 2019/03/18 00:00 [revised]
PHST- 2019/03/24 00:00 [accepted]
PHST- 2019/04/07 06:00 [pubmed]
PHST- 2020/02/13 06:00 [medline]
PHST- 2019/04/07 06:00 [entrez]
AID - S0167-5273(18)36512-4 [pii]
AID - 10.1016/j.ijcard.2019.03.047 [doi]
PST - ppublish
SO  - Int J Cardiol. 2019 Jul 1;286:121-126. doi: 10.1016/j.ijcard.2019.03.047. Epub 
      2019 Mar 26.